ZFIN ID: ZDB-PUB-180830-10
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos
Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S.
Date: 2018
Source: PLoS One   13: e0203087 (Journal)
Registered Authors: Peravali, Ravindra, Spaink, Herman P., Strähle, Uwe
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Antithyroid Agents/pharmacology*
  • Automation, Laboratory*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical/methods*
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Image Processing, Computer-Assisted
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Microscopy, Fluorescence
  • Thyroid Gland/drug effects
  • Thyroid Gland/metabolism
  • Zebrafish
PubMed: 30157258 Full text @ PLoS One
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ABSTRACT
The knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.
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